Towards a better understanding of cueing for Parkinson’s disease | Validation of experimental approaches, and neural insights from healthy individuals
Janne Heijs is a PhD student in the department Biomedical Signals and Systems. (Co)Promotors are dr.ir. T. Heida and prof.dr. R.J.A. van Wezel from the faculty of Electrical Engineering , Mathematics and Computer Science, University of Twente.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting over 11 million people worldwide. Due to the degeneration of dopaminergic neurons in the basal ganglia, people with PD suffer from impaired automatic motor control. A particularly disabling symptom is freezing of gait (FOG), a brief episodic inability to initiate or continue walking, which greatly increases fall risk and reduces quality of life. While pharmacological and surgical treatments provide only partial relief, behavioural compensation strategies such as external cueing are commonly used. External cueing can improve gait and alleviate FOG through rhythmic auditory, visual, or tactile stimuli. However, the effectiveness of cueing varies across individuals and cue types. A deeper understanding of the neural mechanisms underlying different external cueing strategies may help explain this variability.
This thesis addresses methodological challenges in studying the (neural) mechanisms underlying external cueing in individuals with PD. Specifically, this thesis focuses on two key objectives: (1) to validate tools and paradigms for research that enable deeper investigation into the (neural) mechanisms underlying FOG and cueing (Chapters 2-4), and (2) to explore how various cue characteristics influence behaviour and cortical activity during finger tapping in healthy individuals (Chapter 5).
The heterogeneity and unpredictable, episodic nature of FOG complicates the evaluation of FOG and the effects of cueing, especially in clinical or research environments. Experimental setups attempt to induce FOG using triggers. In Chapter 2, we validated the Auditory Stroop task (AST) as a dual-task paradigm to increase cognitive load during walking, while enabling the simultaneous evaluation of visual cues. In healthy elderly, the AST significantly affected all gait parameters, and to a greater extent than the commonly used random numbers task. In people with PD, the AST affected all gait parameters but did not increase FOG severity. Visual cues reduced the AST-induced reduction in stride length in both groups. We concluded that the AST is well-suited to enhance cognitive load during gait experiments with and without visual cues, although it does not reliably provoke FOG episodes.
Gait paradigms such as repetitive finger tapping or foot pedalling have been used to study gait-related brain function, for example, in fMRI scanners. While auditory and proprioceptive cues can be easily integrated, spatial visual cues are more challenging to implement. In Chapter 3, we validated a visual cueing virtual environment (VE) paradigm for use in future neuroimaging studies on motor timing and scaling in persons with PD experiencing FOG. Participants, in a supine position, used alternating foot pedal presses to move through a virtual corridor with either no cues, transverse bars, or staircases. Contrary to expectations, the visual VE cues did not improve motor arrest severity (as a proxy for FOG) or motor timing and scaling in PD. In healthy elderly, the cues modulated pedal amplitude. We could not validate the visual cueing VE paradigm for foot pedalling.
Unlike fMRI, EEG can measure brain activity during actual gait. However, conventional EEG systems require extensive preparation by trained personnel, which is tiring for patients, reduces the duration of actual testing, and limits their use in home-like settings. In Chapter 4, we validated soft, multipin dry EEG electrodes by comparing their performance and signal quality to conventional gel EEG electrodes in healthy individuals. Although the dry EEG system had a lower signal-to-noise ratio, preparation time was significantly reduced, and both systems yielded highly comparable results across time-, frequency-, and spatial-domain measures. We concluded that soft, multipin dry EEG electrodes can be used with similar accuracy as conventional gel electrodes in seated tasks.
The variability in PD and FOG pathology, as well as individual differences in cueing responses, makes it difficult to identify the neural mechanisms underlying various cue characteristics. Studying these mechanisms in healthy individuals first may clarify the fundamental processes of sensorimotor synchronization. In Chapter 5, we performed an EEG study to explore how various cue characteristics influence behaviour and movement-related cortical beta activity in (non-)motor areas during sensorimotor synchronization (SMS). Healthy individuals performed finger tapping with external cues varying in frequency, modality, and rhythmicity. Our results showed a shift from discrete to continuous movement processing with slow versus fast cue frequencies. Auditory cues enabled more accurate synchronization than visual cues and engaged premotor areas more strongly for sensory guidance of movement. Polyrhythmic cues induced widespread right-hemispheric beta suppression, indicating bottom-up control, whereas isorhythmic cues enhanced frontoparietal beta activity, reflecting top-down control of movement. Overall, this study showed that cue characteristics shape motor behaviour and neural processes, suggesting distinct movement control strategies depending on cue frequency, modality, and rhythmicity.
